Group 3 Innate Lymphoid Cells Exacerbate Lupus Nephritis by Promoting B Cell Activation in Kidney Ectopic Lymphoid Structures.

Group 3 innate lymphoid cells (ILC3s) represent a new population in immune regulation, yet their role in lupus nephritis (LN) remains elusive. In the present work, systemic increases in ILC3s, particularly in the kidney, are observed to correlate strongly with disease severity in both human and murine LN. Using MRL/lpr lupus mice and a nephrotoxic serum-induced LN model, this study demonstrates that ILC3s accumulated in the kidney migrate predominantly from the intestine. Furthermore, intestinal ILC3s accelerate LN progression, manifested by exacerbated autoimmunity and kidney injuries. In LN kidneys, ILC3s are located adjacent to B cells within ectopic lymphoid structures (ELS), directly activating B cell differentiation into plasma cells and antibody production in a Delta-like1 (DLL1)/Notch-dependent manner. Blocking DLL1 attenuates ILC3s' effects and protects against LN. Altogether, these findings reveal a novel pathogenic role of ILC3s in B cell activation, renal ELS formation and autoimmune injuries during LN, shedding light on the therapeutic value of targeting ILC3s for LN.

Neural synchrony underlies the positive effect of shared reading on children's language ability.

Although it is well recognized that parent-child shared reading produces positive effects on children's language ability, the underlying neurocognitive mechanisms are not well understood. Here, we addressed this issue by measuring brain activities from mother-child dyads simultaneously during a shared book reading task using functional near infrared spectroscopy hyperscanning. The behavioral results showed that the long-term experience of shared reading significantly predicted children's language ability. Interestingly, the prediction was moderated by children's age: for older children over 30 months, the more the shared reading experience, the better the language performance; for younger children below 30 months, however, no significant relationship was observed. The brain results showed significant interpersonal neural synchronization between mothers and children at the superior temporal cortex, which was closely associated with older children's language ability through the mediation of long-term experience of shared reading. Finally, the results showed that the instantaneous quality of shared reading contributed to children's language ability through enhancing interpersonal neural synchronization and increasing long-term experience. Based on these findings, we tentatively proposed a theoretical model for the relationship among interpersonal neural synchronization, shared reading and children's language ability. These findings will facilitate our understanding on the role of shared reading in children's language development.

Biosynthesis and polyketide oxidation of Monascus red pigments in an integrated fermentation system with microparticles and surfactants.

Monascus red pigments are widely used in the food industry, mainly as intracellular red pigments. The low yields of extracellular red pigments (ERPs) make them unsuitable for large-scale industrial production. Herein, a novel integrated fermentation system (IFS) consisting of sodium starch octenyl succinate and Triton X-100 was explored for increasing yield, resulting in an ERP yield of 126.7 U/mL, 82.6% higher production than controls (69.4 U/mL). Major ERP components in control fermentations were monascopyridine A and monascopyridine B, but dehydro derivatives, rubropunctamine and monascorubramine, predominated in the test fermentations, presumably due to polyketide oxidation induced by Triton X-100. Improvement of hyphal morphology, membrane permeability, respiratory activity, and gene expression for red pigment biosynthesis is likely to be critical to increase yield and change the compositions. This study provides an effective strategy to accelerate the biosynthesis and secretion of Monascus pigments.

[Emerging pathogenic role of group 3 innate lymphoid cells in inflammatory diseases].

Group 3 innate lymphoid cells (ILC3) as a family member of innate lymphoid cells (ILCs), have been defined as novel innate immune cells in the past decade. ILC3 include a variety of heterogenous subsets with different phenotypes and functions, which are mainly distributed in barrier organs such as the intestine, lung and skin. They play an important role in immune regulation, tissue repair and lymphoid tissue formation. However, in various inflammatory diseases, ILC3 become dysregulated and participate in the pathogenesis through secreting a series of cytokines such as interleukin (IL)-17, IL-22, interferon-γ (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) to modulate other immune cells and induce the formation of ectopic lymphoid structures. Therefore, it is of great significance to explore the phenotype and function of ILC3 in order to advance the understanding of inflammatory diseases and find new therapeutic targets. In this article, the phenotypic characteristics, biological functions and research progress of ILC3 in inflammatory diseases were reviewed.

Ultraviolet-Cured Semi-Interpenetrating Network Polymer Electrolytes for High-Performance Quasi-Solid-State Lithium Metal Batteries.

Solid polymer electrolytes with relatively low ionic conductivity at room temperature and poor mechanical strength greatly restrict their practical applications. Herein, we design semi-interpenetrating network polymer (SNP) electrolyte composed of an ultraviolet-crosslinked polymer network (ethoxylated trimethylolpropane triacrylate), linear polymer chains (polyvinylidene fluoride-co-hexafluoropropylene) and lithium salt solution to satisfy the demand of high ionic conductivity, good mechanical flexibility, and electrochemical stability for lithium metal batteries. The semi-interpenetrating network has a pivotal effect in improving chain relaxation, facilitating the local segmental motion of polymer chains and reducing the polymer crystallinity. Thanks to these advantages, the SNP electrolyte shows a high ionic conductivity (1.12 mS cm-1 at 30 °C), wide electrochemical stability window (4.6 V vs. Li+ /Li), good bendability and shape versatility. The promoted ion transport combined with suppressed impedance growth during cycling contribute to good cell performance. The assembled quasi-solid-state lithium metal batteries (LiFePO4 /SNP/Li) exhibit good cycling stability and rate capability at room temperature.

Association between periodontitis and systemic lupus erythematosus: a meta-analysis.

OBJECTIVE: The objective of this study was to explore the association between periodontitis and systemic lupus erythematosus (SLE). METHODS: To identify eligible studies, the PubMed, EMBASE and Web of Science databases were searched from inception to 19 September 2019. Associations of periodontitis, and other periodontal parameters, with SLE were assessed. RESULTS: Ten studies involving 80,633 subjects were included in this meta-analysis. Pooled data showed a significant association between periodontitis and SLE (odds ratio=5.32, 95% confidence interval (CI) 1.69-16.78, p = 0.004). In addition, SLE patients had a higher prevalence of bleeding on probing (mean difference = 0.03, 95% CI 0.00-0.06, p = 0.02) and higher mean clinical attachment loss (mean difference = 0.69, 95% CI 0.39-1.00, p < 0.001). However, there were no significant differences between SLE and reference subjects in mean plaque index, gingival index, pocket depth or decayed, missing or filled teeth. CONCLUSIONS: This study demonstrates a significant association between periodontitis and SLE, which indicates that avoidance of periodontitis by maintaining oral health may be a simple and economical way to prevent SLE.

Comparative functional genomics of the acarbose producers reveals potential targets for metabolic engineering.

The α-glucosidase inhibitor acarbose is produced in large-scale by strains derived from Actinoplanes sp. SE50 and used widely for the treatment of type-2 diabetes. Compared with the wild-type SE50, a high-yield derivative Actinoplanes sp. SE50/110 shows 2-fold and 3-7-fold improvement of acarbose yield and acb cluster transcription, respectively. The genome of SE50 was fully sequenced and compared with that of SE50/110, and 11 SNVs and 4 InDels, affecting 8 CDSs, were identified in SE50/110. The 8 CDSs were individually inactivated in SE50. Deletions of ACWT_4325 (encoding alcohol dehydrogenase) resulted in increases of acarbose yield by 25% from 1.87 to 2.34 g/L, acetyl-CoA concentration by 52.7%, and PEP concentration by 22.7%. Meanwhile, deletion of ACWT_7629 (encoding elongation factor G) caused improvements of acarbose yield by 36% from 1.87 to 2.54 g/L, transcription of acb cluster, and ppGpp concentration to 2.2 folds. Combined deletions of ACWT_4325 and ACWT_7629 resulted in further improvement of acarbose to 2.83 g/L (i.e. 76% of SE50/110), suggesting that the metabolic perturbation and improved transcription of acb cluster caused by these two mutations contribute substantially to the acarbose overproduction. Enforced application of similar strategies was performed to manipulate SE50/110, resulting in a further increase of acarbose titer from 3.73 to 4.21 g/L. Therefore, the comparative genomics approach combined with functional verification not only revealed the acarbose overproduction mechanisms, but also guided further engineering of its high-yield producers.

Improving acarbose production and eliminating the by-product component C with an efficient genetic manipulation system of Actinoplanes sp. SE50/110.

The α-glucosidase inhibitor acarbose is commercially produced by Actinoplanes sp. and used as a potent drug in the treatment of type-2 diabetes. In order to improve the yield of acarbose, an efficient genetic manipulation system for Actinoplanes sp. was established. The conjugation system between E. coli carrying ØC31-derived integrative plasmids and the mycelia of Actinoplanes sp. SE50/110 was optimized by adjusting the parameters of incubation time of mixed culture (mycelia and E. coli), quantity of recipient cells, donor-to-recipient ratio and the concentration of MgCl2, which resulted in a high conjugation efficiency of 29.4%. Using this integrative system, a cloned acarbose biosynthetic gene cluster was introduced into SE50/110, resulting in a 35% increase of acarbose titer from 2.35 to 3.18 g/L. Alternatively, a pIJ101-derived replicating plasmid combined with the counter-selection system CodA(sm) was constructed for gene inactivation, which has a conjugation frequency as high as 0.52%. Meanwhile, almost all 5-flucytosine-resistant colonies were sensitive to apramycin, among which 75% harbored the successful deletion of targeted genes. Using this replicating vector, the maltooligosyltrehalose synthase gene treY responsible for the accumulation of component C was inactivated, and component C was eliminated as detected by LC-MS. Based on an efficient genetic manipulation system, improved acarbose production and the elimination of component C in our work paved a way for future rational engineering of the acarbose-producing strains.

[Effects of essential periodontal treatment on serum level of sCD40L and periodontal clinical parameters in patients with moderate to severe periodontitis at high risk of stroke].

PURPOSE: To investigate the effect of periodontal treatment on patients with moderate to severe periodontitis at high risk of stroke, by detecting the level of serum soluble cell differentiation antigen 40 ligand (sCD40L) before and after periodontal non-surgical treatment. METHODS: Seventy-six patients with moderate to severe periodontitis at high risk of stroke were collected and randomly divided into 2 groups, 40 patients in group A received essential periodontal treatment + routine maintenance therapy, 36 cases in group B only received routine maintenance therapy. Another 36 patients with moderate and severe periodontitis were selected as group C, and received essential periodontal treatment. Bleeding on probing (BOP), periodontal probing depth (PD) and attachment loss (AL) in 6 loci were examined by the same dentists, and enzyme linked immunosorbent assay (ELISA) was used to detect the level of serum sCD40L before treatment and 3 months after treatment. The data were analyzed by SPSS 17.0 software package. RESULTS: Compared with pre-treatment, serum level of sCD40L and periodontal clinical indexes of the three groups decreased. Compared with group B, serum SCD40L in group A significantly decreased(P<0.05). CONCLUSIONS: Periodontal treatment can reduce the serum level of sCD40L in patients with moderate to severe periodontitis at high risk of stroke, and improve the patient's inflammatory state. To a certain extent, periodontal treatment may reduce the risk of high-risk stroke population to develop stroke.